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67th Annual Meeting Abstracts
Prostaglandin Production by Interstitial Cells of Cajal Regulates Spontaneous Rhythmic Contraction of the Urinary Bladder
*Aaron Stike, *Corey Johnson, Adam Klausner, *Vikram Sabarwal, *Amy Miner, Harry Koo, *Paul Ratz
Virginia Commonwealth University, Richmond, VA
Introduction:
Prostaglandins (PGs) are suggested to cause spontaneous rhythmic contractions (SRC) in detrusor smooth muscle (DSM). Patients with overactive bladder (OAB) display elevated SRC. Cyclooxygenase (COX)-1 and COX-2 produce PGs. We determined that bladder interstitial cells of Cajal (ICC) express both COX isotypes. Elevated SRC in OAB is associated with elevated COX activity.
Materials & Methods:
Rabbit DSM strips free of underlying urothelium were incubated in a physiological salt solution (PSS) with or without the non- selective COX inhibitor, ibuprofen, the selective COX 1 inhibitor, SC-560, and the selective COX 2 inhibitor, NS-398. Enzyme immunoassays were used to measure PG production. The subsequent bioassay included the addition of the ventral aspect of the bladder. Indomethacin and SC-51089, a PGE2 antagonist, were drugs utilized in this phase.
Results:
Analysis revealed a 2.5 fold increase in PG production and 4.8 fold increase in PGE2 production. In the PG group ibuprofen reduced production by 56%. Reduction in PGE2 production was seen among all 3 COX inhibitors. Consistent qualitative results indicate a complete inhibition of SRC with indomethacin and the return of rhythm with addition of “superfustate” from the isolated ventral DSM.
Conclusions:
PGs, specifically PGE2, were produced by DSM strips. Ibuprofen inhibited PG production. PGE2 production was inhibited by ibuprofen and low concentrations of COX 1 inhibitor. The COX2 inhibitor demonstrated a strong trend towards inhibiting PGE2 production. Our preliminary bioassay results revealed trends similar to those previously obtained. These results are a step forward in discovering novel rational therapies targeting OAB.
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